Oral JAK1-selective inhibitor for rheumatoid arthritis (RA)

AbbVie announced positive top-line results from the Phase III SELECT-MONOTHERAPY clinical trial of ABT 494 (upadacitinib) an investigational oral JAK1-selective inhibitor, as a monotherapy treatment in patients with moderate to severe rheumatoid arthritis (RA) who did not adequately respond to treatment with methotrexate. Results showed that after 14 weeks of treatment, both once-daily doses of upadacitinib (15 mg and 30 mg) met the study's primary endpoints of ACR20** and low disease activity (LDA)*** versus continuing prior stable methotrexate therapy.

The study showed that at week 14, 68/42/23 percent of patients switched to 15 mg once-daily upadacitinib and 71/52/33 percent of patients switched to 30 mg once-daily upadacitinib achieved an ACR20/50/70** response, compared to 41/15/3 percent of patients continuing on methotrexate. These results were statistically significant (p<0.001 for all comparisons) compared to patients who continued on their baseline methotrexate dose. Both doses also achieved all ranked and all key secondary endpoints.

Additionally, a significantly higher proportion of upadacitinib patients in both dose groups achieved LDA and clinical remission targets at week 14 compared to patients continuing on methotrexate (p<0.001). Low disease activity was achieved by 45 percent and 53 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 19 percent of patients continuing on methotrexate. Clinical remission was achieved by 28 percent and 41 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 8 percent of patients continuing on methotrexate. In this study, the safety profile of upadacitinib was consistent with previously reported Phase III SELECT clinical trials and Phase II studies. Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

Comment: Further results of SELECT-MONOTHERAPY, the third of six studies in the SELECT rheumatoid arthritis clinical trial program, will be presented at a future medical meeting and published in a peer-reviewed publication.